A single miniature endoscope capable of concurrently probing multiple contrast mechanisms of tissue in high resolution is highly attractive, as it makes it possible for providing complementary, more complete tissue information on internal organs hard to access. Here we describe such a miniature endoscope only 1 mm in diameter that integrates photoacoustic imaging (PAI), optical coherence tomography (OCT), and ultrasound (US). The integration of PAI/OCT/US allows for high-resolution imaging of three tissue contrasts including optical absorption (PAI), optical scattering (OCT), and acoustic properties (US). We demonstrate the capabilities of this trimodal endoscope using mouse ear, human hand, and human arteries with atherosclerotic plaques. This 1-mm-diameter trimodal endoscope has the potential to be used for imaging of internal organs such as arteries, GI tracts, esophagus, and prostate in both humans and animals.

In this Letter, we present a photoacoustic imaging (PAI) system based on a low-cost high-power miniature light emitting diode (LED) that is capable of in vivo mapping vasculature networks in biological tissue. Overdriving with 200 ns pulses and operating at a repetition rate of 40 kHz, a 1.2 W 405 nm LED with a radiation area of 1000  μm×1000  μm and a size of 3.5  mm×3.5  mm was used to excite photoacoustic signals in tissue. Phantoms including black stripes, lead, and hair were used to validate the system in which a volumetric PAI image was obtained by scanning the transducer and the light beam in a two-dimensional x-y plane over the object. In vivo imaging of the vasculature of a mouse ear shows that LED-based PAI could have great potential for label-free biomedical imaging applications where the use of bulky and expensive pulsed lasers is impractical.

In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

We describe a novel dual-modality imaging approach that integrates diffuse optical tomography (DOT) and photoacoustic imaging (PAI) through a miniaturized handheld probe based on microelectromechanical systems (MEMS) scanning mirror. We validate this dual-modal DOT/PAI approach using extensive phantom experiments, and demonstrate its application for tumor imaging using tumor-bearing mice systematically injected with targeted contrast agents.

In this Letter, we present a novel tri-modal miniature side-view probe, through which optical-resolution photoacoustic microscopy (OR-PAM), optical coherence tomography (OCT), and pulse-echo ultrasound (US) images can be coaxially acquired and displayed simultaneously. The probe consists of a common optical path for OR-PAM (light delivery) and OCT (light delivery/detection), and a 40-MHz unfocused ultrasound transducer for OR-PAM (photoacoustic detection) and US (ultrasound transmission/receiving) with an overall diameter of 2 mm. Combining OR-PAM, OCT, and US would provide complementary information including optical absorption (OR-PAM), optical back-scattering (OCT), and deep tissue structures (US) about biological tissue. Based on an integrated imaging system consisting of OR-PAM, time-domain OCT, and US, phantom images and in vivo images of rat ear were acquired to demonstrate the capabilities of the integrated tri-modality imaging probe. The probe yields a lateral resolution of 13.6 μm for OR-PAM and OCT, and an axial resolution of 43 μm for OR-PAM and US. Currently, for a scanning area of 1 ×1  mm, it took ∼25  min to acquire data for tri-modal volumetric imaging.

Photoacoustic imaging (PAI) is drawing extensive attention and gaining rapid development as an emerging biomedical imaging technology because of its high spatial resolution, large imaging depth, and rich optical contrast. PAI has great potential applications in endoscopy, but the progress of endoscopic PAI was hindered by the challenges of manufacturing and assembling miniature imaging components. Over the last decade, microelectromechanical systems (MEMS) technology has greatly facilitated the development of photoacoustic endoscopes and extended the realm of applicability of the PAI. As the key component of photoacoustic endoscopes, micromachined ultrasound transducers (MUTs), including piezoelectric MUTs (pMUTs) and capacitive MUTs (cMUTs), have been developed and explored for endoscopic PAI applications. In this article, the recent progress of pMUTs (thickness extension mode and flexural vibration mode) and cMUTs are reviewed and discussed with their applications in endoscopic PAI. Current PAI endoscopes based on pMUTs and cMUTs are also introduced and compared. Finally, the remaining challenges and future directions of MEMS ultrasound transducers for endoscopic PAI applications are given.

We describe a multispectral continuous-wave diffuse optical tomography (DOT) system that can be used for in vivo three-dimensional (3-D) imaging of seizure dynamics. Fast 3-D data acquisition is realized through a time multiplexing approach based on a parallel lighting configuration - our system can achieve 0.12ms per source per wavelength and up to 14Hz sampling rate for a full set of data for 3-D DOT image reconstruction. The system is validated using both static and dynamic tissue-like phantoms. An initial in vivo experiment using a rat model of seizure is also demonstrated.

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